ANALYSIS OF GAMMA-AMINOBUTYRIC ACIDB RECEPTOR FUNCTION IN THE INVITRO AND INVIVO REGULATION OF ALPHA-MELANOTROPIN-STIMULATING HORMONE-SECRETION FROM MELANOTROPE CELLS OF XENOPUS-LAEVIS

The activity of many endocrine cells is regulated by gamma-aminobutyric acid (GABA). The effects of GABA are mediated by GABA(A) and/or GABA, receptors. While GABA(B) receptors in the central nervous system have now been extensively characterized, little is known of the function and pharmacology of GABA(B) receptors on endocrine cells. In the amphibian Xenopus laevis, GABA inhibits the release of alphaMSH from the endocrine melanotrope cells through both GABA(A) and GABA(B) receptors. We have investigated the following aspects of the GABA(B) receptor of the melanotrope cells of X. laevis: 1) the pharmacology of this receptor, using antagonists previously established to demonstrate GABA(B) receptors in the mammalian central nervous system; 2) the relative contribution to the regulation of hormone secretion by the GABA(A) and GABA(B) receptors on melanotrope cells in vitro; and 3) the role of the GABA(B) receptor with respect to the physiological function of the melanotrope cell in vivo, i.e. regulation of pigment dispersion in skin melanophores in relation to background color. Our results demonstrate that phaclofen, 2-hydroxysaclofen, and 4-aminobutylphosphonic acid dow-dependently blocked the inhibition of alphaMSH release by GABA(B) receptor activation, but not by GABA(A) receptor activation. The GABA(B) receptor antagonist delta-aminovaleric acid appeared to be a selective agonist on the GABA(B) receptor of melanotrope cells. The inhibitory secretory response to a low dose of GABA (10(-5) M) was not affected by bicuculline, but was significantly reduced by phaclofen, indicating that at a low GABA concentration, the GABA(B) receptor mechanism would dominate in inhibiting the melano-trope cells. Different thresholds of activation may form the basis for differential action of GABA through both GABA receptor types. The tonic inhibition of alphaMSH release in animals adapted to a white background was not affected by 4-aminobutylphosphonic acid, indicating that the GABA(B) receptor is not (solely) involved in the in vivo inhibition of alphaMSH release in animals on a white background.